The intraocular compartments are protected by a blood-ocular barrier which is actually a composite system formed by the blood-retinal and blood-aqueous barriers. In diabetic retinopathy there are alterations in these blood-ocular barrier systems which include a general increase in passive permeability as well as changes in specific transport processes. The overall goals of this project are to determine the mechanisms and the locations of altered blood-ocular barrier peermeability in early diabetes that may lead to the frank retinopathy of later diabetes. We plan to investigate in vivo the effect of streptozocin-induced diabetes on the permeability characteristics of the blood-ocular barriers using a recently developed radiotracer technique. This technique will be used to study the location, magnitude and time course of changes in the passive permeability of the blood-ocular barriers. We will also investigate in vivo changes in the specific transport system for organic acids known to exist in the blood-retinal barrier. Changes in this system during diabetes have been proposed as the cause of increased fluorescein uptake measured by vitreous fluorophotometry. The mechanism and site of these alterations will be investigated in diabetic rats using the organic acid, radiolabeled p-aminohippurc acid. If these studies confirm a specific effect of diabetes on transport of organic acids across the blood-retinal barrier, then the mechanism of damage will be further elucidated by studying the efflux across the blood-retinal and blood-aqueous barrier of p-aminohippuric acid after a bolus of radiolabeled substance.